In analytical chemistry, liquid and gas chromatography techniques have become important tools in the identification of chemical sample components. The basic principle underlying all chromatographic techniques is the separation of a sample chemical mixture into individual components by transporting the mixture in a moving fluid through a porous retentive media. The moving fluid is referred to as the mobile phase and the retentive media has been referred to as the stationary phase. One of the differences between liquid and gas chromatography is that the mobile phase is either a liquid or a gas, respectively.
In a gas chromatograph, typically, a supply of inert carrier gas (mobile phase) is continually passed as a stream through a heated column containing porous sorptive media (stationary phase). GC columns have also been known to comprise a hollow capillary tube having an inner diameter in the range of few hundred microns. A sample of the subject mixture is injected into the mobile phase stream and passed through the column. As the subject mixture passes through the column, it separates into its various components. Separation is due primarily to differences in the volatility characteristics of each sample component with respect to the temperature in the column. A detector, positioned at the outlet end of the column, detects each of the separated components as they exit the column.
The analytical choice between liquid and gas chromatography techniques is largely dependent on the molecular weight of the compound being analyzed. Liquid chromatographs are capable of analyzing much heavier compounds than gas chromatographs. However, since gas chromatography detection techniques are more sensitive, they are preferred. Consequently, a need exists for a chromatographic device which is as sensitive as a GC device and is capable of analyzing compounds having heavier molecular weights than those now subject to GC analysis.
The advent of Supercritical Fluid Chromatography (SFC) provided a potential bridge between gas and liquid chromatography advantages, i.e., high sensitivity and heavier molecular weight samples. In SFC, a fluid heated above the critical point, is used as the mobile phase. Such fluid is passed under pressure through a media which differentially retains sample components. As the pressure of the mobile phase is increased, for example, from about 40 ATM to approximately 400 ATM, the sample being analyzed separates into its various components dependent upon the relative differential solubility of each component with the mobile phase. Since the mobile phase is a gas, detectors used in GC can be utilized, significantly enhancing detection sensitivity and selectivity.
SFC has been found to be primarily useful in the analysis of moderate molecular weight homologous series (M.W. 100 to 10,000) and some thermally labile molecules such as pesticides and pharmaceuticals. The problem with SFC, however, is the long period of time involved in conducting a sample analysis. Consequently, it is still desireable to provide a chromatographic device having the speed of GC techniques and which are capable of analyzing higher molecular weight compounds.
The present invention satisfies the above described need of increasing the speed and extending the molecular weight range of compounds capable of GC analysis by providing apparatus and methods which control the carrier gas (mobile phase) pressure in relation to programmed flow and temperature parameters in an open loop arrangement.
It has been known in the past to program temperature in gas chromatographic analyzation since separation of the sample components is due primarily to differences in the volatility characteristics of each component with respect to the temperature in the column. By raising the column temperature either in a constant linear fashion or in a variable non-linear fashion over a sufficient range of temperature one can assure high resolution detection of all sample components in a minimized time period. High resolution is assured because each component is emerging from the column at its optimum temperature.
As used herein the term resolution refers to the distinctness of graphed peaks generated by known detection apparatus, wherein each peak is representative of the detection of a sample component.
It has also been known in the past that the time required for a temperature programmed GC analysis can be reduced even further if carrier gas flow is programmed. Scott, R. P. W., New Horizons in Column Performance, 5th International Symposium on Gas Chromatography as reported in Gas Chromatography 1964 by Goldup, pp. 32-37 indicates that analysis time can be reduced by increasing the flow rate. However, while increasing the flow rate may reduce analysis time, efficiency is also reduced due to so-called overloaded components which results in poor resolution at detection. By customizing the temperature and flow programs for particular mixtures so that flow is increasing during the detection of the overloaded components, the reduction in efficiency was said to be overcome somewhat.
Costa Neto, C., et al., Programmed Flow Gas Chromatography, Journal of Chromatography, Vol. 15 (1964) pp. 301-313 discusses the utilization of a programmed flow of GC mobile phase in isothermic or temperature programmed runs, in order to obtain the separation of complex mixtures. Theoretical derivations of equations relating flow rate to various chromatogram properties such as peak migration, peak width, peak area and peak height are discussed. Flow rate in relation to efficiency and resolution is also discussed. The programmed flow actually used by the authors was said to be manual in nature using a step valve.
Zlatkis, A., Flow Programming--A New Technique in Gas Chromatography, Journal of Gas Chromatography (Mar. 1965), pp. 75-81 discusses the use of a pneumatically regulated flow controller for regulating flow rate in an exponential fashion between preset limits. In reviewing previous flow programming reports, such as the Costa Neto reference discussed above, Zlatkis et al. characterizes that reference as only discussing flow programming in relation to so called preparative gas chromatography as opposed to practical analytical gas chromatography.
Nygren, S. et al., Flow Programming in Glass Capillary Column-Electron Capture Gas Chromatography by Using the Valve in the Splitter Line, Journal of Chromatography, Vol. 123 (1976) pp. 101-108 discusses flow programming through the use of a metering valve in the side outlet of an inlet splitter. It was said that by exponentially programming carrier gas flow, under certain circumstances, results could be achieved which were comparable to temperature programming.
More recently, Larson, J. R. et al., Flow Programming System for Process Capillary Gas Chromatography, Journal of Chromatography, Vol. 405 (1987) pp. 163-168 discusses a continuous flow programming technique for process capillary gas chromatography which processes do not have temperature programming capabilities. It was concluded that by programming carrier gas flow in a process GC application, shorter cycle times could be achieved than temperature programmed GC devices.
The problem with each of the above flow programming devices lies in that carrier gas flow and/or temperature programming are independently operated, i.e. closed loop systems. As such, these systems are operated exclusive of each other. Such devices cannot assure constant column efficiency or constant mass flow. The major drawbacks of such closed loop flow control systems are limited dynamic range, the need for flow sensing and changes or drifts in the calibration of the flow sensor. Changes or drift in calibration can be caused by the contamination of the flow sensor.
Additionally, such independently operated closed loop systems are incapable of detecting undesirable conditions affecting the accuracy of the chromatographic analysis and of making adjustments to avoid such conditions. For example, for a given temperature program, a desired flow characteristic may not be possible within the GC system parameters. The above described devices are not capable of determining or sensing the failure of the device to achieve the desired flow characteristic.
It has been discovered that through the use of the open loop flow control system of the present invention, not only can the problems of prior temperature and flow programming devices be overcome, but also, the molecular weight range of compounds capable of GC analysis can be extended. As used in this application the phrase open loop flow control system signifies that there is no direct feedback of the controlled parameter. In open loop flow control there is no flow sensing operation, only pressure sensing and computation of desired pressure to give calculated flow.